This is a competitive renewal grant request for continued studies of vasculitis, a disease of humans frequently associated with collagen-vascular type autoimmune diseases. The murine model to be exploited is one in which splenic cells are co-cultured in vitro with syngeneic microvascular smooth muscle (SM) followed by transfer of the activated (immunized) cells into syngeneic recipients resulting in a distinct vasculitis. Preliminary studies have shown strong MHC restriction (syngeneic response much greater than allogeneic) governing spleen cell activation to SM that can be blocked by anti-Ia in vitro. The hypothesis to be tested is that lymphocytes recognize SM and MHC antigens in vitro to become activated. After transfer into syngeneic hosts the lymphocytes recruit cells that also recognize SM and MHC antigens in attacking vascular SM. This proposal will address both the in vitro lymphocyte activation events as well as the in vivo effector events in the host mice. Specific aims related to in vitro events include determination of mRNA for class 11 antigen in SM with the use of cDNA probes and determination of whether SM can present antigen to antigen-specific T cell clones. Specific aims related to the effector (in vivo) events include determination of the possible role of SM specific antibodies in affected mice and determination of the effector cell(s) in the lesions by light and electron microscopy. Several SM activated lymphocyte clones (L3 T4+ and Lyt 2+) have been developed and will be used to determine their ability to elicit vasculitis as well as their specificity for SM.